title: Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity.
abstract: The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Iwasaki
authors.forename: Ken
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Kana
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kawana
authors.forename: Taneaki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D015519:Bone Density / Q000235:genetics; D002459:Cell Fusion; D006706:Homeostasis; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000494:pharmacology
chemical_list: D000199:Actins; C499636:DC-STAMP protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse